Plant‐derived alkaloid sinomenine potentiates glucocorticoid pharmacodynamics in mitogen‐activated human peripheral blood mononuclear cells by regulating the translocation of glucocorticoid receptor

Autor: Kentaro Sugiyama, Wencheng Xu, Yuanchao Tu, Haruki Yamada, Toshihiko Hirano, Sachiko Tanaka, Hiroshi Masaki, Xiaoqin Wang, Kenji Onda
Rok vydání: 2018
Předmět:
Zdroj: Phytotherapy Research. 33:187-196
ISSN: 1099-1573
0951-418X
Popis: Sinomenine has been used as an antirheumatic drug in China. Glucocorticoid combined with sinomenine could be an alternative therapeutic approach. In this study, we evaluated the sinomenine potential effect on glucocorticoid pharmacodynamics in vitro using a human peripheral blood mononuclear cell (PBMC) culture system. We also disclosed the possible action mechanism of sinomenine with a focus on P-glycoprotein function and glucocorticoid receptor (GR) translocation into nucleus. The median (range) of methylprednisolone IC50 values against the PBMC proliferation was 3.18 (0.45-6.81) ng/mL, whereas the median (range) IC50 values of methylprednisolone combined with 0.03, 0.3, 3, and 30 μM sinomenine were 1.85 (0.05-5.15), 0.83 (0.10-3.90), 0.56(0.09-1.62), and 0.59(0.05-1.30) ng/mL, respectively. Sinomenine significantly decreased the IC50 values of methylprednisolone and enhanced the immunosuppressive effect of methylprednisolone (p < 0.05). Sinomenine alone regulated the GR translocation in both Jurkat T cells and normal human PBMCs, and the combination of sinomenine and methylprednisolone showed stronger GR-modulatory activity than methylprednisolone alone. Thus, the additive effect of sinomenine to promote the methylprednisolone immunosuppressive efficacy was suggested to be related to nuclear GR-translocation. However, sinomenine did not significantly inhibit the P-glycoprotein function in the activated PBMCs, suggesting that sinomenine's additive effect seemed to be unrelated with the P-glycoprotein inhibition.
Databáze: OpenAIRE
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